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Stem Cell Reports. 2013 Dec 12;1(6):575-89. doi: 10.1016/j.stemcr.2013.10.012. eCollection 2013.

Human developmental chondrogenesis as a basis for engineering chondrocytes from pluripotent stem cells.

Author information

1
Department of Orthopaedic Surgery, Orthopedic Hospital Research Center, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, USA.
2
Department of Orthopaedic Surgery, Orthopedic Hospital Research Center, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, USA ; Laboratorio de Biología del Desarrollo Celular, Laboratorios de Investigación Aplicada en Nuerociencias, Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia, Escobar B1625XAF, Buenos Aires, Argentina.
3
Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, USA.
4
Broad Stem Cell Research Center, University of California at Los Angeles, Los Angeles, CA 90095, USA.
5
Broad Stem Cell Research Center, University of California at Los Angeles, Los Angeles, CA 90095, USA ; Department of Medicine and Physiology, Cardiovascular Research Laboratory, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, USA.
6
Laboratorio de Biología del Desarrollo Celular, Laboratorios de Investigación Aplicada en Nuerociencias, Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia, Escobar B1625XAF, Buenos Aires, Argentina.
7
Department of Orthopaedic Surgery, Orthopedic Hospital Research Center, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, USA ; Department of Molecular, Cell and Developmental Biology, University of California at Los Angeles, Los Angeles, CA 90095, USA.
8
Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, USA ; Broad Stem Cell Research Center, University of California at Los Angeles, Los Angeles, CA 90095, USA ; Jonsson Comprehensive Cancer Center, University of California at Los Angeles, Los Angeles, CA 90095, USA.
9
Novogenix Laboratories, LLC, Los Angeles, CA 90033, USA.
10
Department of Orthopaedic Surgery, Orthopedic Hospital Research Center, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, USA ; Broad Stem Cell Research Center, University of California at Los Angeles, Los Angeles, CA 90095, USA ; Jonsson Comprehensive Cancer Center, University of California at Los Angeles, Los Angeles, CA 90095, USA.

Abstract

Joint injury and osteoarthritis affect millions of people worldwide, but attempts to generate articular cartilage using adult stem/progenitor cells have been unsuccessful. We hypothesized that recapitulation of the human developmental chondrogenic program using pluripotent stem cells (PSCs) may represent a superior approach for cartilage restoration. Using laser-capture microdissection followed by microarray analysis, we first defined a surface phenotype (CD166(low/neg)CD146(low/neg)CD73(+)CD44(low)BMPR1B(+)) distinguishing the earliest cartilage committed cells (prechondrocytes) at 5-6 weeks of development. Functional studies confirmed these cells are chondrocyte progenitors. From 12 weeks, only the superficial layers of articular cartilage were enriched in cells with this progenitor phenotype. Isolation of cells with a similar immunophenotype from differentiating human PSCs revealed a population of CD166(low/neg)BMPR1B(+) putative cartilage-committed progenitors. Taken as a whole, these data define a developmental approach for the generation of highly purified functional human chondrocytes from PSCs that could enable substantial progress in cartilage tissue engineering.

PMID:
24371811
PMCID:
PMC3871393
DOI:
10.1016/j.stemcr.2013.10.012
[Indexed for MEDLINE]
Free PMC Article

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